Studies of chemical disposition are designed to provide both applied knowledge of the fate of chemicals in the intact animal in support of toxicity tests conducted by the National Toxicology Program and basic knowledge of mechanisms of chemical toxicity. Thus, objectives of these studies are two-fold. Each study is designed to address those physical and chemical properties unique to the compound studies as well as to provide data which will permit structural characterization of the respective chemical class. Each study is also designed to address the impact of one or more factors such as dose, age, sex, or route of exposure on the toxicity of the chemical(s) studies and the significance of this data to assessments of human health risks. Studies conducted during the current year have addressed the fate and mechanisms of toxicity of tris(2-chloroethyl)phosphate (TRCP) and benzyltrimethylammonium chloride (BTMAC). TRCP is a flame retardant, used in many consumer produts which was recently reported by the NTP to be a kidney carcinogen in rats. Studies completed during this year have determined that sex-related variations such as metabolism, clearance and concentration dependent toxicity do not account for the sex-dependent dofferences in carcinogenic responses observed in the bioassay. Results of these studies further indicate that administration of TRCP results in increased cell proliferation in the outer margin of the renal medula. This is the same area of the kidney in which yumors were observed in the bioassay. However, cell proliferation was equally pronounced in male and femal rats indicating that factors in addition to or in combination with cell proliferation may account in the greater development of tumors in the kidneys of male over female rats. BTMAC is a quarternary ammonium compound which is used extensively in the chemical manufacturing industry. Previous studies indicate that is has significant neurotoxicity. Ongoing studies of the metabolism and disposition of BTMAC indicate that it is readily absorbed from the gastrointestinal tract, subject to little metabolism and is rapidly cleared from the body. Rats excrete BTMAC primarily in urine as the parent compound. Results of these studies indicate that toxicity from this compound can most probably be attributed to the parent compound and since BTMAC appears to have little potential for bioaccumulation, any toxicity observed is likely to be limited to acute toxicity.